Opioid-Related Disorders
Conditions
Brief summary
To determine the relative abuse potential of VYCAVERT (hydrocodone bitartrate and acetaminophen) compared to GENERIC H/A (hydrocodone bitartrate and acetaminophen) when crushed and administered intranasally to non dependent, recreational opioid users.
Interventions
DRUGPlacebo taken first
Snorted in both nostrils within 5 minutes; 48 hours washout between doses
DRUGGeneric H/A taken first
Snorted in both nostrils within 5 minutes; 48 hours washout between doses
DRUGVycavert taken first
Snorted in both nostrils within 5 minutes; 48 hours washout between doses
DRUGGeneric H/A plus i taken first
Snorted in both nostrils within 5 minutes; 48 hours washout between doses
DRUGGeneric H/A plus p taken first
Snorted in both nostrils within 5 minutes; 48 hours washout between doses
Sponsors
Acura Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests. 2. Subject is a recreational opioid user who is NOT dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM IV TR) criteria. A recreational opioid user is defined as a user of opioids for non medical purposes (i.e., for psychoactive effects) on at least 10 occasions within the last year and at least once in the 12 weeks before the Screening Visit (Visit 1). 3. Subjects must have experience with intranasal opioid administration, defined as intranasal use on at least 3 occasions within the last year before Screening. 4. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs). 5. Subject is able to speak, read, and understand English sufficiently to comprehend the nature of the study and to understand the informed consent form (ICF) and consent process. 6. An informed consent document signed and dated by the subject. 7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. \-
Exclusion criteria
1. Diagnosis of substance and/or alcohol dependence (excluding caffeine and nicotine), as assessed by the Investigator using the DSM IV TR criteria. 2. Has participated in, is currently participating in, or is seeking treatment for substance and/or alcohol related disorders (excluding nicotine and caffeine). 3. Has a positive urine drug screen (UDS) including tetrahydrocannabinol (THC) at Screening (Visit 1). NOTE: Subjects with an opioid positive or THC-positive UDS at Visit 1 may be re tested once on or before Visit 2 (Day 0). If the UDS re test is negative, the subject can proceed to Visit 2. A positive UDS at Visit 2 will exclude the subject from further participation, unless the UDS is THC-positive in which the subject can continue in the study at the discretion of the Investigator. 4. Has a positive alcohol breath test at Screening. Positive results may be repeated and/or subjects re scheduled at the Investigator's discretion. 5. Has any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, suspected of having paralytic ileus). 6. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emax - Maximum Drug Liking | 8 hours | Do you dislike or like the drug effect you are feeling now? The question is scored using a 100-point bipolar visual analog scale (VAS) anchored in the center with neither like nor dislike (score of 50), on the left with Strong Disliking (score of 0) and on the right with Strong Liking (score of 100). Maximum Score. Assessment were made at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 8 hours post-dosing. |
Countries
United States
Participant flow
Recruitment details
44 recreational drug users with snorting experience were enrolled with 40 completing-Crossover designed
Pre-assignment details
Each subject had to pass a blinded snorted drug discrimination phase to meet enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Taken First followed by all other doses crossover | 8 |
| Generic H/A Taken First followed by all other doses crossover | 8 |
| Vycavert Taken First followed by all other doses crossover | 8 |
| Generic H/A Plus i Taken First followed by all other doses crossover | 8 |
| Generic H/A Plus p Taken First followed by all other doses crossover | 8 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Generic H/A Taken First | Vycavert Taken First | Generic H/A Plus i Taken First | Placebo Taken First | Generic H/A Plus p Taken First | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 40 Participants |
| Age, Continuous | 24.4 years STANDARD_DEVIATION 3.99 | 24.4 years STANDARD_DEVIATION 3.99 | 24.4 years STANDARD_DEVIATION 3.99 | 24.4 years STANDARD_DEVIATION 3.99 | 24.4 years STANDARD_DEVIATION 3.99 | 24.4 years STANDARD_DEVIATION 3.99 |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 40 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 44 | 0 / 44 | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 4 / 44 | 5 / 44 | 13 / 44 | 18 / 44 | 5 / 44 |
| serious Total, serious adverse events | 0 / 44 | 0 / 44 | 0 / 44 | 0 / 44 | 0 / 44 |
Outcome results
Primary
Emax - Maximum Drug Liking
Do you dislike or like the drug effect you are feeling now? The question is scored using a 100-point bipolar visual analog scale (VAS) anchored in the center with neither like nor dislike (score of 50), on the left with Strong Disliking (score of 0) and on the right with Strong Liking (score of 100). Maximum Score. Assessment were made at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 8 hours post-dosing.
Time frame: 8 hours
Population: Completers of all doses per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Emax - Maximum Drug Liking | 54.5 score on a scale | Standard Deviation 8.52 |
| Generic H/A | Emax - Maximum Drug Liking | 75.0 score on a scale | Standard Deviation 11.81 |
| Vycavert | Emax - Maximum Drug Liking | 72.1 score on a scale | Standard Deviation 12.98 |
| Generic H/A Plus i | Emax - Maximum Drug Liking | 75.6 score on a scale | Standard Deviation 12.48 |
| Generic H/A Plus p | Emax - Maximum Drug Liking | 73.0 score on a scale | Standard Deviation 13.13 |